BackgroundThe reduced treatment time of dental implants with immediate loading protocol is an appealing solution for dentists and patients. However, there remains a significant risk of early peri-implant bone response following the placement of immediately loaded implants, and limited information is available regarding loading directions and the associated in vivo characteristics of peri-implant bone during the early stages. This study aimed to investigate the effects of immediate loading directionality on the expression of mechanical sensing protein PIEZO1 and the healing process of peri-implant bone in the early stage.MethodsThirty-two implants were inserted into the goat iliac crest models with 10 N static lateral immediate loading applied, followed by histological, histomorphological, immunohistochemical, X-ray microscopy and energy dispersive X-ray spectroscopy evaluations conducted after 10 days.ResultsFrom evaluations at the cellular, tissue, and organ levels, it was observed that the expression of mechanical sensing protein PIEZO1 in peri-implant bone was significantly higher in the compressive side compared to the tensile side. This finding coincided with trends observed in interfacial bone extracellular matrix (ECM) contact percentage, bone mass, and new bone formation.ConclusionsThis study provides a novel insight into the immediate loading directionality as a potential influence factor for dental implant treatments by demonstrating differential effects on the mechanical sensing protein PIEZO1 expression and related early-stage healing processes of peri-implant bone. Immediate loading directions serve as potential therapeutic influence factors for peri-implant bone during its early healing stage.